The potency of anesthetic agents to inhibit the ability of a patient to respond with movement to painful stimuli has long been used as a test of anesthetic action. This potency, characterized by its ED50, is widely known as the minimum alveolar concentration (MAC). Several lines of evidence have shown that spinal NMDA receptor activation might play a key role in the processing of nociceptive information1,29-30 and in the determination of the MAC of inhalational anesthetics.31-33 For example, the NMDA receptors are distributed mainly in the superficial laminae of the spinal cord.12,28 Both repetitive C-fiber stimulation and direct application of glutamate or NMDA produce spinal neuronal sensitization and enhance responsiveness, which can be blocked by NMDA receptor antagonists.1,34-36 Behavioral studies demonstrate that spinal administration of NMDA produces thermal hyperalgesia, caudally directed scratching and biting, and exaggerated responsiveness to light touch.8,37-39 Moreover, antagonism of the spinal NMDA receptors produces antinociception in numerous animal models of pain39-44 and reduction in the MAC of isoflurane.31-33 However, the molecular mechanisms underlying these actions remain unknown. The postsynaptic density (PSD), a highly organized cytoskeletal structure found adjacent to the postsynaptic membrane of excitatory synapses, is believed to play a role in the organization of receptors and related proteins involved in synaptic signaling.45-55 A number of proteins enriched in the PSD have been characterized.47-48 One of these proteins, postsynaptic density-95 (PSD-95)/synapse-associated protein-90 (SAP90), is an abundant scaffolding molecule that binds and clusters the NMDA receptor preferentially at synapses in the brain and spinal cord.3,4,5,7,9,49 This raises the possibility that PSD-95/SAP90 might be involved in many physiological and pathophysiologic actions triggered via the NMDA and perhaps other receptors in the central nervous system. Indeed, suppression of PSD-95/SAP90 expression attenuated excitotoxicity produced via NMDA receptor activity in brain neurons.23 The lack of PSD-95/SAP90 revealed an enhanced NMDA-dependent long-term potentiation and impaired learning.16 
The role of the N-methyl-D-aspartate (NMDA) receptor in spinal hyperalgesia has been demonstrated by behavioral, electrophysiological and neurochemical findings.1,8,21,26 However, the molecular mechanisms underlying these actions are unclear. The NMDA receptor consists of two distinct types of subunits: NMDAR1 (NR1) and NMDAR2A-D (NR2A-D).19 The C-termini of the NR2 subunits interact with PSD-95/SAP90 and other members of the membrane-associated guanylate kinase (MAGUK) family in the brain2,6,9,10,17,20 This raises the possibility that the sensory hyperalgesia produced through NMDA receptor activation is determined by NMDA receptor-bound proteins of the MAGUK family in the spinal cord.
There is a need in the art for new ways of treating and preventing hyperalgesia and chronic and acute pain. In addition, there is a need in the art for new and safer ways of rendering patients unconscious via general anesthesia or by sedating them.